New therapeutic agents against triple negative breast cancer – targeting an unmet clinical need with the second generation pol i inhibitor, pmr-116.

Website Queen's University Belfast

Last Day to Apply: 31 October 2024

Project description:
This project aims to develop novel therapies for triple-negative breast cancer by combining novel and old drugs to enhance treatment efficacy and reduce side effects.

Breast Cancer (BCa) is a heterogeneous disease with various molecular subtypes and associated outcomes, currently the most common malignancy worldwide. Triple-negative breast cancer (TNBC) accounts for 15-20% of all BCa, and has the highest rates of distant relapse (~50%) and mortality. Treatment of TNBC is challenged by its lack of specific targets. The newest therapeutic advances, such as PARP inhibitors, antibody-drug conjugates, and immune checkpoint inhibitors, offer no benefit to the majority of TNBC patients. This underscores the urgency for novel precision therapies to improve outcomes for TNBC patients.

One such opportunity involves 2nd-generation Pol I transcription inhibitor (PMR-116) and the first-in-class pan-inhibitor of KDM4 histone demethylase (TACH101). These compounds are currently in Phase 1 clinical trials for advanced solid tumours, including TNBC and other metastatic BCa (ACTRN12620001146987 and NCT05076552, respectively). Preliminary data from the KP lab show synergy between epirubicin and PMR-116. Furthermore, knockdown of histone demethylase KDM4 appears to sensitise TNBC cells to Pol I inhibition, revealing an opportunity to enhance the efficacy of Pol I inhibition, by incorporating the KDM4 inhibitor TACH101 into the treatment regime. Combined, this can enable the development of effective treatments which could reduce anthracycline doses, reducing its adverse effects.

The KP lab’s exclusive access to PMR-116, commercial availability of TACH101 and access to established preclinical, orthotopic, immune competent TNBC models (CB lab), and TNBC expertise in biomarker development (PM)will enable this multidisciplinary team to:

(1) Determine the efficacy of the PMR-116 and epirubicin combination in treating TNBC (CB lab)
(2) Explore and validate the effect of KDM4 inhibition by TACH101 on PMR-116 efficacy (KP lab)
(3) Identify predictive biomarkers for treatment response and prognosis (PM lab).

This research projects investigates the clinical properties of new anticancer drugs in combination with well-established ones or with other novel drugs have the potential to discover synergistic effects that enhance treatment efficacy, reduce side effects, and overcome drug resistance. This aligns with Queen’s ambition to “shape a better world through life-changing education and research” and its commitment to “address real-world needs” through high-impact research”. This interdisciplinary collaboration, in the area of One Health, with Hannan group, ANU and Pimera Inc, USA will enhance the impact of this project’s outputs and supports the University’s goal of driving social and economic change with global resonance, reinforcing Queen’s position as a leader in innovative healthcare research and clinical excellence.

Entrance Requirements
The minimum academic requirement for admission to a research degree programme is normally an Upper Second Class Honours degree in a relevant subject from a UK or ROI HE provider, or an equivalent qualification acceptable to the University. Further information can be obtained by contacting the School.

International Students
For information on international qualification equivalents, please check the specific information for your country.

English Language Requirements:
Evidence of an IELTS* score of 6.5, with not less than 5.5 in any component, or an equivalent qualification acceptable to the University is required (*taken within the last 2 years).

International students wishing to apply to Queen’s University Belfast (and for whom English is not their first language), must be able to demonstrate their proficiency in English in order to benefit fully from their course of study or research. Non-EEA nationals must also satisfy UK Visas and Immigration (UKVI) immigration requirements for English language for visa purposes.

For more information on English Language requirements for EEA and non-EEA nationals see:

If you need to improve your English language skills before you enter this degree programme, INTO Queen’s University Belfast offers a range of English language courses. These intensive and flexible courses are designed to improve your English ability for admission to this degree.

Fees and funding:

1 EU citizens in the EU Settlement Scheme, with settled or pre-settled status, are expected to be charged the NI or GB tuition fee based on where they are ordinarily resident, however this is provisional and subject to the publication of the Northern Ireland Assembly Student Fees Regulations. Students who are ROI nationals resident in GB are expected to be charged the GB fee, however this is provisional and subject to the publication of the Northern Ireland Assembly student fees Regulations.

2 It is expected that EU students who are ROI nationals resident in ROI will be eligible for NI tuition fees. The tuition fee set out above is provisional and subject to the publication of the Northern Ireland Assembly student fees Regulations.

3 EU Other students (excludes Republic of Ireland nationals living in GB, NI or ROI) are charged tuition fees in line with international fees.

All tuition fees quoted are for the academic year 2021-22, and relate to a single year of study unless stated otherwise. Tuition fees will be subject to an annual inflationary increase, unless explicitly stated otherwise.

Biological Sciences costs
Students may incur additional costs for small items of clothing and/or equipment necessary for lab or field work

Additional course costs

All Students
Depending on the programme of study, there may also be other extra costs which are not covered by tuition fees, which students will need to consider when planning their studies . Students can borrow books and access online learning resources from any Queen’s library. If students wish to purchase recommended texts, rather than borrow them from the University Library, prices per text can range from £30 to £100. Students should also budget between £30 to £100 per year for photocopying, memory sticks and printing charges. Students may wish to consider purchasing an electronic device; costs will vary depending on the specification of the model chosen. There are also additional charges for graduation ceremonies, and library fines. In undertaking a research project students may incur costs associated with transport and/or materials, and there will also be additional costs for printing and binding the thesis. There may also be individually tailored research project expenses and students should consult directly with the School for further information.

Bench fees:
Some research programmes incur an additional annual charge on top of the tuition fees, often referred to as a bench fee. Bench fees are charged when a programme (or a specific project) incurs extra costs such as those involved with specialist laboratory or field work. If you are required to pay bench fees they will be detailed on your offer letter. If you have any questions about Bench Fees these should be raised with your School at the application stage. Please note that, if you are being funded you will need to ensure your sponsor is aware of and has agreed to fund these additional costs before accepting your place.

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